Thesis (Ph. D.)--University of Washington, 2005.In this study, I have attempted to understand how Notch signals promote different stages of T cell maturation by examining the regulation of Notch signals on two levels. First, I have used an in vitro culture system to examine how differential signals through 2 classes of Notch ligands, Jagged and Delta, influence thymocyte differentiation. These data reveal that Notch signals inhibit B cell development and promote the maturation of immature thymocytes in two separable stages. While both classes of Notch ligands are able to inhibit B cell development, only Delta is able to promote the proliferation of immature thymocytes. Second, I have examined how Deltex, an intracellular modulator of Notch signals, regulates Notch signals by generating mice that are deficient in two of the three known Deltex homologues. Although there is considerable evidence that over-expression of Deltex in hematopoietic stem cells can inhibit Notch signals, and that Deltex is highly expressed in developing thymocytes, my data reveals that expression of Deltex in T cell progenitors is not essential for regulating the early stages of T cell maturation
